Erratum: Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies

Reid, Michelle D.; Bağcı, Pelin; Ohike, Nobuyuki; Saka, Burcu; Seven, İpek Erbarut; Dursun, Nevra; Balcı, Serdar; Güçer, Hasan; Tajiri, Takuma; Basturk, Olca; Kong, So Yeon; Goodman, Michael; Akkaş, Gizem; Adsay, Volkan

doi:10.1038/modpathol.2015.124

Cited by 25 publications

(8 citation statements)

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“…13 However, both mitotic index and Ki-67 measurements are susceptible to sampling issues, interpretation errors, and may not truly reflect the clinical behaviour of these neoplasms as WHO grade 1 tumours can also develop distant metastases. 14 15 Thus, additional biomarkers are needed to improve the prognostic classification and management of patients.…”

Section: Introductionmentioning

confidence: 99%

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size

Hackeng

Brosens

Kim

et al. 2021

Gut

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ObjectiveRecent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown.DesignAn international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS).ResultsATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%).ConclusionsATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

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Section: Introductionmentioning

confidence: 99%

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size

Hackeng

Brosens

Kim

et al. 2021

Gut

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“…In NET cases where the Ki67 index was close to the cutoffs, high magnification (400×) microphotographs of the hot spots were taken. The captured images were then analyzed manually on a printed copy [32]. A Ki67 index > 20% was a necessary requisite for pdNEC definition, in addition to a poorly differentiated histologic structure.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up

et al. 2018

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Background: Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. Methods: Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. Results: Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. Conclusions: Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease.

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“…The perceived advantages and disadvantages of each counting method are summarised in Table 2. To date, manual counting is considered to be the gold standard method to count the Ki67 proliferation index in neuroendocrine neoplasms 5,10,11 . It is highly accurate, readily available, permitting inclusion/exclusion of specific areas and allowing case‐based adjustment of positive threshold.…”

Section: Discussionmentioning

confidence: 99%

“…Various digital image analysis platforms and machine learning (ML)-based algorithms have shown to be highly sensitive and specific to obtain an automatic reading of the Ki67 index in pancreatic neuroendocrine neoplasms and breast carcinomas. [5][6][7][8][9][10][11] The utility of these platforms in determining the Ki67 index in MTC is yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms

Nadeem,

Hanna,

Viswanathan

et al. 2023

Histopathology

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AimsThe International Medullary Thyroid Carcinoma Grading System, introduced in 2022, mandates evaluation of the Ki67 proliferation index to assign a histological grade for medullary thyroid carcinoma. However, manual counting remains a tedious and time‐consuming task.Methods and resultsWe aimed to evaluate the performance of three other counting techniques for the Ki67 index, eyeballing by a trained experienced investigator, a machine learning‐based deep learning algorithm (DeepLIIF) and an image analysis software with internal thresholding compared to the gold standard manual counting in a large cohort of 260 primarily resected medullary thyroid carcinoma. The Ki67 proliferation index generated by all three methods correlate near‐perfectly with the manual Ki67 index, with kappa values ranging from 0.884 to 0.979 and interclass correlation coefficients ranging from 0.969 to 0.983. Discrepant Ki67 results were only observed in cases with borderline manual Ki67 readings, ranging from 3 to 7%. Medullary thyroid carcinomas with a high Ki67 index (≥ 5%) determined using any of the four methods were associated with significantly decreased disease‐specific survival and distant metastasis‐free survival.ConclusionsWe herein validate a machine learning‐based deep‐learning platform and an image analysis software with internal thresholding to generate accurate automatic Ki67 proliferation indices in medullary thyroid carcinoma. Manual Ki67 count remains useful when facing a tumour with a borderline Ki67 proliferation index of 3–7%. In daily practice, validation of alternative evaluation methods for the Ki67 index in MTC is required prior to implementation.

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Erratum: Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies

Cited by 25 publications

References 14 publications

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms

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